The invention concerns an analytical flow cell with a planar film sensor comprising a cell volume in contact with the film sensor, an input line to this cell volume and the sensor, and an output line for through-flow of a fluid medium to be analyzed. The invention further concerns a film sensor for such an analytical flow cell.
Analytical flow cells with film sensors, especially with thin-film electrodes, are known, and are commonly used now in, for example, gas chromatography or HPLC detectors. Film sensors are also often particularly suitable for miniaturization, and so are suitable for use in miniaturized analytical systems (e. g., xe2x80x9clab-on-a-chipxe2x80x9d systems). Here, a detector is considered to be a unit of the actual analytical cell with the sensor and an electronic measuring unit, such as a potentiostat and a signal amplifier. Use of thin film sensors or thin film electrodes in the analytical cell has provided significant advantages for analytical technology. It makes further miniaturization possible, and can make a substantial saving in sensor material. That has led to decidedly more economical measurement cells when the electrode materials are expensive, such as platinum or gold. Thin-film sensors have film thicknesses in the range of nanometers to micrometers. Thick-film sensors with film thicknesses in the micrometer range are being used for certain purposes.
The printed 3-electrode pattern is currently the standard for electrochemical thin-film cells. In such cells the working electrode, reference electrode and auxiliary electrode are printed, with quite varied patterns, and contacts are applied to a carrier. The thin-film or thick-film electrode pattern can also be produced in other manners. Various processes are available for that.
The analytical, or measurement cell, also called a thin-film cell, comprises a cell volume on the electrode side of the carrier, past the electrode, to hold the fluid medium to be analyzed, such as a liquid in HPLC or gas in GC, as well as an inlet and an outlet allowing the medium to flow through, so that the cell is made as a flow cell. Cell volumes are currently generally from one to a few microliters. Cell volumes in the nanoliter region are possible today.
Aside from various electrode geometries, quite varied cell patterns have already been tested and used to attain the best possible flow properties and high sensitivity with the best possible resolution. Dead volumes should be avoided. In one of the cell patterns now in use, the medium being analyzed, i. e., the mobile phase, the mobile phase is directed obliquely in a jet onto the thin film, and removed obliquely again on the opposite side. Another possibility is that of directing the medium being investigated perpendicularly onto the electrode, as much as possible at a point, and removing it at the sides.
In examination of liquids, another problem arises because gases dissolved in the liquid can separate easily at solid surfaces, forming small gas bubbles on the electrode or electrodes during operation. That causes signal distortion and impairs the measurement.
The objective of the invention is to design an analytical flow cell of the type stated initially, and a corresponding film sensor, so as to attain high sensitivity with good resolution even at small cell volumes and, in particular, to avoid formation of bubbles by separation of gases from the liquid being examined at the electrodes or, generally, at the sensor.
To reach this objective, the invention provides for an analytical flow cell with a planar sensor in contact with the cell volume, and an inlet to this cell volume and to the sensor, and an outlet to allow fluid flow, that the sensor has at least one defined passage transverse to the sensor film for fluid medium being analyzed so that the input and outlet are on opposite sides of the film.
The accompanying film sensor for the analysis flow cell according to the invention is correspondingly characterized by the fact that the sensor has at least one defined passage transverse to the sensor film for the passage of a fluid medium to be analyzed.
A xe2x80x9cdefined passagexe2x80x9d in the terminology used in this application, is an opening adapted to the cell geometry, which forms a short channel through the sensor film, transverse to the film, and, optionally, through an underlying carrier.
It was found, surprisingly, that substantial advantages for measurement technology appear if the fluid medium being analyzed is conducted xe2x80x9cthrough the electrode toward the backxe2x80x9d. Because of the thinness of a film sensor, contact times are short, so that resolution is good. The fluid medium can be moved through the cell by pressure or suction. That also allows potential technological variations not possible with other cell geometries. The amount of gas bubbles forming on the film sensor is distinctly reduced. The new geometry also makes it possible to keep the active cell volume of the flow cell considerably smaller and to avoid dead volumes for the most part.
The cell volume can be adapted to the type of measurement to be done. For instance, the cell volume on the sensor, which makes contact possible between the fluid medium and the sensor, can be designed approximately cylindrical with the axis of the cylinder perpendicular to the sensor film; or it can have approximately conical geometry, with the base of the cone adjacent to the sensitive surface of the film sensor and the tip of the one opening into the inlet. Various cell volumes, larger or smaller in the general range of a few nanoliters up to about 50 microliters, can be produced. There can also be a collecting volume acting as a buffer volume for the fluid medium directly behind the sensor.
The measurement can optionally be multiplied in the form of several parallel or series measurements by use of multiple inputs and outlets and several electrodes.
The analytical flow cell can also advantageously be integrated into a holder which combines all the components of the cell. The holder comprises connections for input and output of the medium being analyzed, and for conducting the signals obtained with the sensor to a detector unit. The holder also comprises means to pick off signals from the sensor which are preferably conducted to a plug as a connector, from which they can be taken off with the usual connecting means, as well as means for separably mounting the sensor in a position in contact with the cell volume.
For the latter, the holder can comprise at least parts separably connected, between which the sensor is placed or mounted in a combination held together by its shape, or clamped. The two separably connected parts can advantageously be connected with a joint or a clamp so that the holder with at least 2 parts can be unfolded. That makes it possible to change the film sensor, which is printed on a carrier with the contacts, in a particularly simple manner. Alternatively, the sensor can be solidly integrated in a unit so that it is not replaceable but is instead firmly combined with the analysis unit, i.e., the microsystem. For instance, it can be completely welded all around, between films, for instance.
The holder can be made of metal or plastic or other suitable material such as ceramic. In one preferred embodiment, the entire cell geometry with the cell volume, collecting volume optionally placed behind the sensor, inputs, outlets, feed and return connections, is integrally formed in this holder. That is, for instance, it is milled from the holder material, or combined into a fluidic part placed in the holder.
Other preferred embodiments are those in which the film sensor is not replaceable, but instead is integrated into a miniaturized analytical system (xe2x80x9cmicrosystemxe2x80x9d) such as a xe2x80x9clab-on-a-chipxe2x80x9d system. Then, for example, the sensor can be heat-sealed inside a microsystem, as stated above. xe2x80x9cLab-on-a-chipxe2x80x9d is the term for miniaturized analytical systems. They are also called xcexcTAS, xe2x80x9cmicro total analysis systemsxe2x80x9d. Advances in microtechnology and progress in integration of microelectronic circuits will in the near future provide complete analytical stations in extremely small spaces which may be of postage stamp size, for instance. These xe2x80x9claboratoriesxe2x80x9d on a chip can be made with mass production processes from the semiconductor, plastics, and printing industries. Thus they are optimally suited as disposable systems in the mass markets of the life sciences (health, nutrition, environment) to improve our quality of life.
Thus the film sensor can be integrated into an analytical station assembled as a unit, which contains other components, such as a pump to supply the liquids being examined, as well as channels in which the purified or chemically converted fluid flows.
As such a system must be very small, and must be produced very economically, it will, among other things, not have any replaceable parts. The film sensor according to the invention is therefore preferably solidly integrated into the flow channel system (for instance, printed onto a plastic part which simultaneously contains the channel).
The film sensor itself which, according to the invention, has at least one defined passage for flow or a fluid medium being analyzed, transverse to the film, can comprise at least one electrode. Preferably, the sensor comprises a multielectrode pattern printed on a carrier, generally with a working electrode, a reference electrode, and an auxiliary electrode, with at least one of the electrodes having a defined passage transverse to the film. The actual sensitive film, i.e., the thin conductive electrode layer printed onto the carrier can be in the immediate vicinity of the passages, immediately adjacent to them, extending into them, or passing through them, so that the passage or passages always run effectively transverse to the electrode, i.e., to the sensor layer. The electrodes need not all be printed on the same side of the carrier. For example, the working electrode can be in front of the carrier in the direction of flow, with the reference and auxiliary electrodes placed after the carrier in the direction of flow. The film sensor is preferably a thin film sensor.
The sensor can also be a biosensor, preferably comprising a thin film fixed onto a carrier. This thin film can, for instance, be platinum, gold, or graphite, and can be coated with enzymes or other biomaterials such as antibodies.
In general, the sensor can be a biosensor or a chemosensor, such as an ion-selective electrode, a pH electrode, or another electrode. Electrochemical measurements can be done as usual, for instance, potentiometrically, amperometrically, or polarographically.
According to the invention, at least one passage is provided in the sensor or in the electrode. However, there can also be multiple passages with different geometries, so that when multiple electrodes are used there can be one or more passages in various electrodes.
The passages can be in the sensitive layer itself as well as in the immediate vicinity, that is, directly on the layer or adjacent in the same plane, such as in the carrier. In the case of a sensitive layer of carrier and coating, then, the sensitive layer can be immediately beside the passages, which are in any case placed transverse to the entire sensor film, adjacent to them, projecting into them, or passing through them.
The passages are preferably round and of constant diameter through the film thickness. The passages can, though, be arranged transverse to the film conically or in some other suitable geometry.